The objective of the proposed research is to understand the mechanism of the highly specific increase in albumin in kidney basement membranes (glomerular basement membrane, tubular basement membrane) observed by immunofluorescence and quantitative immunoassay in diabetic nephropathy. A similar increase is observed in diabetic muscle capillary and sarcolemmal basement membranes. This study will define whether the increased binding of albumin to basement membranes is a consequence of an alteration in albumin or in renal basement membranes induced by the diabetic state. Diabetic and normal albumin, obtained from sera and kidney eluates, will be evaluated for differences in binding to basement membrane fractions as well as for structural changes. In addition, basement membrane fractions from diabetic kidneys will be studied for changes that lead to increased entrapment of serum proteins. The presence of increased amounts of albumin in basement membranes in kidney may play an important role in the pathogenesis of diabetic renal and vascular disease.